The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes

Abstract

Objective:To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes.Methods:Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data.Results:PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE).Conclusions:Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.

Pregnancy and neonatal outcomes in women with type 1 diabetes mellitus

“…In our study, frequency of preeclampsia was 33 %, which is almost 3 times more frequent than reported 12 % in other studies (11,12).…”

Preeclampsia and Diabetes

“…Smaller longitudinal studies have examined these markers in women with type 1 diabetes who did not have microalbuminuria in early pregnancy [32], women with preexisting diabetes that required insulin [33], and a mixed group of women with type 1 or type 2 diabetes [34]. sFlt-1, sEng and PGF prior to 25 weeks gestation did not differ between diabetic women who developed preeclampsia and those who did not [34, 32, 33].…”

“…sFlt-1, sEng and PGF prior to 25 weeks gestation did not differ between diabetic women who developed preeclampsia and those who did not [34, 32, 33]. After 25 weeks gestation, results were conflicting.…”

Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes

“…Previous studies have shown that women with good blood glucose control, both prior to and during pregnancy, are at a reduced risk of pre-eclampsia, compared to those with poor glycaemic control (Cohen et al, 2014;Holmes et al, 2011). Despite this, the majority of women in the current study did not recall receiving information about the benefits of good glycaemic control on the risk of pre-eclampsia.…”